The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast Cancer
Pyrotinib (PYR) is a pan-HER kinase inhibitor that inhibits signaling via the RAS/RAF/MEK/MAPK and PI3K/AKT pathways. In this study, we aimed to investigate the antitumor efficacy of pyrotinib combined with adriamycin (ADM) and explore its mechanisms on HER2+ breast cancer. We investigated the effec...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.616443/full |
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| author | Chaokun Wang Shuzhen Deng Jing Chen Xiangyun Xu Xiaochen Hu Dejiu Kong Gaofeng Liang Xiang Yuan Yuanpei Li Xinshuai Wang |
| author_facet | Chaokun Wang Shuzhen Deng Jing Chen Xiangyun Xu Xiaochen Hu Dejiu Kong Gaofeng Liang Xiang Yuan Yuanpei Li Xinshuai Wang |
| author_sort | Chaokun Wang |
| collection | DOAJ |
| description | Pyrotinib (PYR) is a pan-HER kinase inhibitor that inhibits signaling via the RAS/RAF/MEK/MAPK and PI3K/AKT pathways. In this study, we aimed to investigate the antitumor efficacy of pyrotinib combined with adriamycin (ADM) and explore its mechanisms on HER2+ breast cancer. We investigated the effects of PYR and ADM on breast cancer in vitro and in vivo. MTT assay, Wound-healing, and transwell invasion assays were used to determine the effects of PYR, ADM or PYR combined with ADM on cell proliferation, migration, and invasion of SK-BR-3 and AU565 cells in vitro. Cell apoptosis and cycle were detected through flow cytometry. In vivo, xenograft models were established to test the effect of PYR, ADM, or the combined therapy on the nude mice. Western blotting was performed to assess the expression of Akt, p-Akt, p-65, p-p65, and FOXC1. The results indicated that PYR and ADM significantly inhibited the proliferation, migration, and invasion of SK-BR-3 and AU565 cells, and the inhibitory rate of the combination group was higher than each monotherapy group. PYR induced G1 phase cell-cycle arrest, while ADM induced G2 phase arrest, while the combination group induced G2 phase arrest. The combined treatment showed synergistic anticancer activities. Moreover, PYR significantly downregulated the expression of p-Akt, p-p65, and FOXC1. In clinical settings, PYR also exerts satisfactory efficacy against breast cancer. These findings suggest that the combination of PYR and ADM shows synergistic effects both in vitro and in vivo. PYR suppresses the proliferation, migration, and invasion of breast cancers through down-regulation of the Akt/p65/FOXC1 pathway. |
| format | Article |
| id | doaj-art-e4c2e09e04c24f92a270164c42ab5416 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-e4c2e09e04c24f92a270164c42ab54162025-08-20T02:56:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.616443616443The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast CancerChaokun Wang0Shuzhen Deng1Jing Chen2Xiangyun Xu3Xiaochen Hu4Dejiu Kong5Gaofeng Liang6Xiang Yuan7Yuanpei Li8Xinshuai Wang9Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaMedical College, Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaMedical College, Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaDepartment of Internal Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, United StatesHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaPyrotinib (PYR) is a pan-HER kinase inhibitor that inhibits signaling via the RAS/RAF/MEK/MAPK and PI3K/AKT pathways. In this study, we aimed to investigate the antitumor efficacy of pyrotinib combined with adriamycin (ADM) and explore its mechanisms on HER2+ breast cancer. We investigated the effects of PYR and ADM on breast cancer in vitro and in vivo. MTT assay, Wound-healing, and transwell invasion assays were used to determine the effects of PYR, ADM or PYR combined with ADM on cell proliferation, migration, and invasion of SK-BR-3 and AU565 cells in vitro. Cell apoptosis and cycle were detected through flow cytometry. In vivo, xenograft models were established to test the effect of PYR, ADM, or the combined therapy on the nude mice. Western blotting was performed to assess the expression of Akt, p-Akt, p-65, p-p65, and FOXC1. The results indicated that PYR and ADM significantly inhibited the proliferation, migration, and invasion of SK-BR-3 and AU565 cells, and the inhibitory rate of the combination group was higher than each monotherapy group. PYR induced G1 phase cell-cycle arrest, while ADM induced G2 phase arrest, while the combination group induced G2 phase arrest. The combined treatment showed synergistic anticancer activities. Moreover, PYR significantly downregulated the expression of p-Akt, p-p65, and FOXC1. In clinical settings, PYR also exerts satisfactory efficacy against breast cancer. These findings suggest that the combination of PYR and ADM shows synergistic effects both in vitro and in vivo. PYR suppresses the proliferation, migration, and invasion of breast cancers through down-regulation of the Akt/p65/FOXC1 pathway.https://www.frontiersin.org/articles/10.3389/fonc.2021.616443/fullHER2 positive breast neoplasmpyrotinibadriamycinsynergisticAkt |
| spellingShingle | Chaokun Wang Shuzhen Deng Jing Chen Xiangyun Xu Xiaochen Hu Dejiu Kong Gaofeng Liang Xiang Yuan Yuanpei Li Xinshuai Wang The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast Cancer Frontiers in Oncology HER2 positive breast neoplasm pyrotinib adriamycin synergistic Akt |
| title | The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast Cancer |
| title_full | The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast Cancer |
| title_fullStr | The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast Cancer |
| title_full_unstemmed | The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast Cancer |
| title_short | The Synergistic Effects of Pyrotinib Combined With Adriamycin on HER2-Positive Breast Cancer |
| title_sort | synergistic effects of pyrotinib combined with adriamycin on her2 positive breast cancer |
| topic | HER2 positive breast neoplasm pyrotinib adriamycin synergistic Akt |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.616443/full |
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